Despite intensive experimental research activities devoted to neuronal injury following cerebral ischemia and trauma, our understanding of the mechanisms by which the neurons undergo necrosis and apoptosis is still rather poor. The objective of our CNS Injury and Edema Research Center is to employ both in vivo models of cerebral ischemia and trauma and in vitro cell culture systems to further elucidate cellular and molecular mechanisms of neuronal cell death. Our long-term goal is to develop pharmacological and therapeutic interventions to ameliorate the brain injuries. We will primarily focus on the role of oxidative stress, novel gene expression, and astrocytes on ischemic dismutase gene will be employed. Thus the research project of this proposal provides for interdisciplinary studies ranging from molecular biology, physiology, molecular genetics, biochemistry and morphology to investigate the basis of ischemic and traumatic brain injury. The program includes four interrelated projects: Oxidative stress and neuronal injury in cerebral ischemia; Role of stress protein and SOD expression on neuronal resistance to ischemia; Mechanism of subarachnoid hemorrhage-induced brain injury after head trauma; and Stress genes in cerebral ischemia. All projects are conceptually integrated with one another. Experimentally, they will rely heavily on the Scientific Core. Extensive utilization of transgenic and knockout mutant mice will provide a common vehicle for our interaction among the projects to study the mechanisms of neuronal injury following cerebral ischemia and trauma.